Triphenylphosphine → tert-butyl (3R,4R)-3-(4-tert-butoxy-benzoylamino)-4-(4-tert-butoxy-benzoyloxy)-azepan-1-carboxylate

HRID 1075485Notes

Reaction equation

HRID 1075485 reaction equation
[C:1]([O:5][C:6]1[CH:29]=[CH:28][C:9]([C:10]([NH:12][C@H:13]2[C@@H:19]([OH:20])[CH2:18][CH2:17][CH2:16][N:15]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:14]2)=[O:11])=[CH:8][CH:7]=1)([CH3:4])([CH3:3])[CH3:2].[C:30]([O:34][C:35]1[CH:43]=[CH:42][C:38]([C:39](O)=[O:40])=[CH:37][CH:36]=1)([CH3:33])([CH3:32])[CH3:31].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1>[C:1]([O:5][C:6]1[CH:29]=[CH:28][C:9]([C:10]([NH:12][C@H:13]2[C@H:19]([O:20][C:39](=[O:40])[C:38]3[CH:37]=[CH:36][C:35]([O:34][C:30]([CH3:32])([CH3:31])[CH3:33])=[CH:43][CH:42]=3)[CH2:18][CH2:17][CH2:16][N:15]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:14]2)=[O:11])=[CH:8][CH:7]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 11776TriphenylphosphineHCID 5353024-tert-Butoxybenzoic AcidHCID 57267698tert-butyl (3R,4S)-3-(4-tert-butoxy-benzoylamino)-4-hydroxy-azepan-1-carboxylate

Product 1

HCID 53735547tert-butyl (3R,4R)-3-(4-tert-butoxy-benzoylamino)-4-(4-tert-butoxy-benzoyloxy)-azepan-1-carboxylateYield 41.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

262 mg of diethyl azadicarboxylate in 2 ml of tetrahydrofuran were added while stirring to 407 mg of the compound prepared in Example 16, 253 mg of 4-(tert-butoxy)-benzoic acid and 394 g of triphenylphosphine in 8 ml of tetrahydrofuran. After stirring at 50° C. for 4hours, the solvent was removed under reduced pressure and the residue was taken up in 20 ml of cyclohexane and washed once with 20 ml of water and twice with 10 ml of 70% methanol/water each time. The aqueous-alcoholic phase was extracted twice with 10 ml of cyclohexane each time. The combined cyclohexane phases were dried over sodium sulphate and the solvent was removed under reduced pressure. The residual viscous oil was dissolved in 10 ml of hot heptane, seeded with pure end product and left to crystallize at room temperature for 18 hours and yielded 241 mg of tert-butyl (3R,4R)-3-(4-tert-butoxy-benzoylamino)-4-(4-tert-butoxy-benzoyloxy)-azepan-1-carboxylate of melting point 126-128° C. This compound can be reacted further as in Example 12b.

Workup

  1. customthe solvent was removed under reduced pressure
  2. washwashed once with 20 ml of water and twice with 10 ml of 70% methanol/water each time
  3. extractionThe aqueous-alcoholic phase was extracted twice with 10 ml of cyclohexane each time
  4. dry with materialThe combined cyclohexane phases were dried over sodium sulphate
  5. customthe solvent was removed under reduced pressure
  6. dissolutionThe residual viscous oil was dissolved in 10 ml of hot heptane
  7. waitleft
  8. customto crystallize at room temperature for 18 hours

Sources & evidence

ORD record
ord-93d1a481c1e8425ea71c054708fb16fa
Source dataset
uspto-grants-1999_05
Patent number
US05902882

Reaction notes

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